Accommodating protein flexibility in computational drug design.

By Heather A. Carlson, James Andrew McCammon. Molecular Pharmacology, 2000

343 citations recorded by the source corpus.

The need to account for the dynamic behavior of a receptor has long been recognized as a complicating factor in computational drug design. The use of a single, rigid protein structure—usually from a high-quality X-ray crystal structure—still is the standard in most applications ([Zheng and Kyle

Subfields: Computational Theory and Mathematics, Materials Chemistry, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ff4c91dfd0d949964f17e4efcfbb261a84963536

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Citations in the corpus

Ligand–protein inverse docking and its potential use in the computer search of protein targets of a small molecule (2001, background): “Protein flexibility is known to influence ligand binding, and thus methods such as side-chain conformational sampling and protein ensemble generation have been explored in docking studies.(34) Limited side-chain conformation sampling is considered in INVDOCK along with additional energy minimization”
Computer-aided drug-discovery techniques that account for receptor flexibility. (2010, positive): “A composite pharmacophore model based on these many characterizations is then generated, and ligand databases are searched for compounds with complementary chemical features [12,15,34].”
Is allostery an intrinsic property of all dynamic proteins? (2004, background): “What then differentiates between allosteric and nonallosteric proteins? Or, are all proteins potentially allosteric and evolution made use of it to its own advantage to regulate and optimize cellular pathways? If so, can drugs be engineered to utilize this property to regulate protein activity? Some”
Principles of docking: An overview of search algorithms and a guide to scoring functions (2002, background): “7 The relevance of using ensembles is also indicated in recent studies showing that even apparently speciﬁc receptors bind a range of ligands of different sizes, shapes, and composition, often with higher afﬁnities than the presumably speciﬁc ligand.”